Gene amplification is often observed in tumor cells. Such amplification constitutes one of the mechanisms of protooncogene activation that influences the progress of tumor (Stark, G. R. et al., Cell, 57, 901–908 (1989)). The identification of amplification of a target gene occurring in the amplified region and the characterization of the same provides important information in clarifying the molecular mechanisms of the development and advancement of cancer.
Esophageal carcinoma is ranked as the sixth cause of deaths due to cancers in the world (Pisani, P. et al., Int. J. Cancer, 83, 18–29 (1999)). The two main histopathological types of tumors found in esophageal cancer tissues are squamous cell carcinoma and adenomatous carcinoma. Squamous cell carcinoma is the type most frequently found in Japan as in other countries (Public Welfare White Paper 1999).
Several gene modifications involved in development, advancement and metastasis of esophageal squamous cell carcinoma (inclusive of amplification of MYC, EGFR and CCND1) have already been identified (Lu, S. H. et al., Int. J. Cancer, 42, 502–505 (1988); Jiang, W. et al., Cancer Res., 52, 2980–2983 (1992)).
Recent studies based on the comparative genomic hybridization technique (CGH; Kallioniemi et al., Science, 258, 818–821 (1992)) have newly revealed at least ten amplification regions in esophageal squamous cell carcinoma (Pack, S. D., Genes Chromosomes Cancer, 25, 160–168 (1999); Shinomiya, T. et al., Genes Chromosomes Cancer, 24, 337–344 (1999); Du Plessis, L. et al., Cancer Res., 59, 1877–1883 (1999)). However, no genes involved in esophageal squamous cell cancer have been identified in those detected chromosomal amplification regions.
The inventors searched for abnormal DNA copy numbers in 29 esophageal squamous cell carcinoma cell lines and, as a result, detected several new amplification regions. These amplification regions can be confirmed in the chromosome region 9p23-24 with high frequency.
On the other hand, a genomic change in the chromosome region 9p23-24 is reported to be associated with various malignancies such as nonsmall cell lung carcinoma, liver carcinoma, ovarian carcinoma, uterine cervix carcinoma, mammary carcinoma, osteosarcoma and mediastinal B cell lymphoma (Knuutila, S. et al., Am. J. Pathol., 152, 1107–1123 (1998)).
Taking this report into consideration, it is inferred that there is a possibility that one or more genes capable of functioning as an oncogene activated by amplification might be found in the above chromosome region 9p23-24, irrespective of tissue type.